Drug delivery device

ABSTRACT

The present disclosure relates to a drug delivery device, comprising a housing adapted to receive a medicament container, a plunger and a plunger release mechanism, the plunger release mechanism comprising a first plunger boss arranged on the plunger, a profiled slot arranged on the housing and adapted to be engaged by the first plunger boss so as to inhibit movement of the plunger in a distal direction, wherein the plunger is rotatable about a longitudinal axis to release the first plunger boss from the profiled slot so as to allow movement of the plunger in the distal direction, a sleeve coupled to the housing to permit movement of the sleeve relative to the housing, wherein a sleeve ramp is arranged on the sleeve, the sleeve ramp adapted to engage a rib or boss on the plunger to rotate the plunger to release the first plunger boss from the profiled slot when the sleeve is moved in a proximal direction.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is the national stage entry of InternationalPatent Application No. PCT/EP2018/079918, filed on Nov. 1, 2018, andclaims priority to Application No. EP 17306523.6, filed on Nov. 3, 2017,the disclosures of which are incorporated herein by reference.

TECHNICAL FIELD

The disclosure generally relates to a drug delivery device having aplunger release mechanism.

BACKGROUND

Drug delivery devices (i.e. devices capable of delivering medicamentsfrom a medication container) typically fall into two categories—manualdevices and auto-injectors.

In a manual device—the user must provide the mechanical energy to drivethe fluid through the needle. This is typically done by some form ofbutton/plunger that has to be continuously pressed by the user duringthe injection. There are numerous disadvantages to the user from thisapproach. If the user stops pressing the button/plunger then theinjection will also stop. This means that the user can deliver anunderdose if the device is not used properly (i.e. the plunger is notfully pressed to its end position). Injection forces may be too high forthe user, in particular if the patient is elderly or has dexterityproblems.

Auto-injectors are devices which completely or partially replaceactivities involved in parenteral drug delivery from standard syringes.These activities may include removal of a protective syringe cap,insertion of a needle into a patient's skin, injection of themedicament, removal of the needle, shielding of the needle andpreventing reuse of the device. This overcomes many of the disadvantagesof manual devices. Injection forces/button extension, hand-shaking andthe likelihood of delivering an incomplete dose are reduced. Triggeringmay be performed by numerous means, for example a trigger button or theaction of the needle reaching its injection depth. In some devices theenergy to deliver the fluid is provided by a spring.

Plunger release mechanisms are applied to control motion of a plunger ina drug delivery device in a manner keeping the plunger in a definedposition until a condition is met suddenly allowing the plunger to movewithin the drug delivery device thus delivering a dose of a drug from asyringe.

SUMMARY

The present disclosure provides a drug delivery device with an improvedplunger release mechanism as well as a method for assembling a drugdelivery device.

According to the present disclosure, a drug delivery device comprises ahousing adapted to receive a medicament container, a plunger and aplunger release mechanism comprising: a first plunger boss arranged onthe plunger, a profiled slot arranged on the housing and adapted to beengaged by the first plunger boss so as to inhibit movement of theplunger in a distal direction, wherein the plunger is rotatable about alongitudinal axis to release the first plunger boss from the profiledslot so as to allow movement of the plunger in the distal direction, asleeve coupled to the housing to permit movement of the sleeve relativeto the housing, wherein a sleeve ramp is arranged on the sleeve, thesleeve ramp adapted to engage a projection such as a rib or boss on theplunger to rotate the plunger to release the first plunger boss from theprofiled slot when the sleeve is moved in a proximal direction.

In an exemplary embodiment, the profiled slot is adapted to induce atorque to the plunger when an axial force is applied to the plunger,wherein the profiled slot comprises at least one angled surface adaptedto engage the first plunger boss to induce a torque in a firstrotational direction to the plunger to release the first plunger bossfrom the profiled slot.

In an exemplary embodiment, the profiled slot further comprises a wallfor limiting movement of the first plunger boss in the first rotationaldirection when engaged to the first angled surface and a second angledsurface adjacent the wall and adapted to induce a torque in the firstrotational direction to the plunger to release the first plunger bossfrom the profiled slot.

This allows for preventing the plunger from being released while thefirst plunger boss is engaged to the first angled surface and the wall.This state is particularly useful for storing and transporting a drugdelivery device or a part thereof comprising the plunger and optionallya drive spring so that the drive spring cannot inadvertently advance theplunger, e.g. if the drug delivery device or the part thereof comprisingthe plunger is dropped. In order to transition the plunger into a statein which it may be released, the plunger may be moved away from thefirst angled surface along the wall and rotated so that the firstplunger boss engages the second angled surface. The transition into thisstate may be performed during final assembly of a drug delivery device.If the plunger is not otherwise prevented from rotating further, thefirst plunger boss may slide down the second angled surface untildisengaging it, allowing the plunger to advance, e.g. for displacing amedicament from a medicament container, in particular a syringe.

In an exemplary embodiment, the plunger may be prevented from rotatingfurther by a sleeve rib on a sleeve which may be moved on contact withan injection site to allow further rotation of the plunger.

In an exemplary embodiment, the drug delivery device may comprise theabove described profiled slot with the first and second angled surfacesand the wall without having a sleeve ramp adapted to engage a projectionsuch as a rib or boss on the plunger.

In an exemplary embodiment, the first angled surface and/or the secondangled surface have/has an angle in a range from 30° to 70° relative toa perpendicular on a longitudinal axis of the plunger.

In an exemplary embodiment, the plunger release mechanism furthercomprises a second plunger boss arranged on the plunger and a sleeve ribarranged on the sleeve, the sleeve rib having a longitudinal faceadapted to engage the second plunger boss preventing rotation of theplunger in the first rotational direction to keep the first plunger bossengaged to the angled surface, wherein the sleeve rib is adapted todisengage the second plunger boss when the sleeve rib is moved in aproximal direction thereby allowing the plunger to rotate in the firstrotational direction and the first plunger boss to disengage the secondangled surface.

In an exemplary embodiment, the plunger release mechanism furthercomprises an angled plunger rib on the plunger adapted to abut thesleeve rib so as to induce a torque to the plunger in the firstrotational direction and push the plunger in the proximal direction whenthe first plunger boss is engaged to the first angled surface and to thewall.

In an exemplary embodiment, the sleeve rib comprises a distal faceadapted to engage the second plunger boss so as to limit movement of thesleeve rib in a distal direction relative to the plunger.

In an exemplary embodiment, the release of the first plunger boss fromthe first angled surface and/or from the second angled surface and/orthe release of the second plunger boss from the sleeve rib provides anaudible feedback.

The sleeve may be adapted to be moved in a proximal direction relativeto the housing upon contact with an injection site to disengage thesleeve rib from the second plunger boss.

In an exemplary embodiment, a drive spring is arranged within thehousing and adapted to bias the plunger in the distal direction fordisplacing a piston of a medicament container.

In an exemplary embodiment, the plunger is hollow and the drive springis arranged within the plunger.

In an exemplary embodiment, the housing comprises a distal region and aproximal region, wherein the proximal region comprises the profiledslot.

In an exemplary embodiment, the angled plunger rib is adapted to abutthe sleeve rib upon coupling of the proximal region with the plunger andthe drive spring to the distal region for moving the first plunger bossfrom the first angled surface to the second angled surface.

In an exemplary embodiment, the drug delivery device comprises amedicament container.

In an exemplary embodiment, the medicament container contains amedicament.

According to an aspect of the present disclosure, a method forassembling a drug delivery device, comprises providing a plunger havinga first plunger boss and an angled plunger rib, providing a housinghaving a profiled slot comprising a first angled surface adapted toengage the first plunger boss to induce a torque in a first rotationaldirection to the plunger, a wall for limiting movement of the firstplunger boss in the first rotational direction when engaged to the firstangled surface and a second angled surface adapted to induce a torque inthe first rotational direction to the plunger, providing a sleeve havinga sleeve rib, inserting the plunger and a drive spring into the housing,rotating the plunger by an angle in a second rotational direction toengage the first plunger boss to the first angled surface and the wall,moving the sleeve in a proximal direction so that the sleeve ribproximally abuts the angled plunger rib thereby inducing a torque to theplunger in the first rotational direction and pushing the plunger in theproximal direction so that the first plunger boss disengages from thewall and engages the second angled surface.

The drug delivery device, as described herein, may be configured toinject a drug or medicament into a patient. For example, delivery couldbe sub-cutaneous, intra-muscular, or intravenous. Such a device could beoperated by a patient or care-giver, such as a nurse or physician, andcan include various types of safety syringe, pen-injector, orauto-injector.

The device can include a cartridge-based system that requires piercing asealed ampule before use. Volumes of medicament delivered with thesevarious devices can range from about 0.5 ml to about 2 ml. Yet anotherdevice can include a large volume device (“LVD”) or patch pump,configured to adhere to a patient's skin for a period of time (e.g.,about 5, 15, 30, 60, or 120 minutes) to deliver a “large” volume ofmedicament (typically about 2 ml to about 5 ml).

In combination with a specific medicament, the presently describeddevices may also be customized in order to operate within requiredspecifications. For example, the device may be customized to inject amedicament within a certain time period (e.g., about 3 to about 20seconds for auto-injectors, and about 10 minutes to about 60 minutes foran LVD). Other specifications can include a low or minimal level ofdiscomfort, or to certain conditions related to human factors,shelf-life, expiry, biocompatibility, environmental considerations, etc.Such variations can arise due to various factors, such as, for example,a drug ranging in viscosity from about 3 cP to about 50 cP.Consequently, a drug delivery device will often include a hollow needleranging from about 25 to about 31 Gauge in size. Common sizes are 27 and29 Gauge.

The delivery devices described herein can also include one or moreautomated functions. For example, one or more of needle insertion,medicament injection, and needle retraction can be automated. Energy forone or more automation steps can be provided by one or more energysources. Energy sources can include, for example, mechanical, pneumatic,chemical, or electrical energy. For example, mechanical energy sourcescan include springs, levers, elastomers, or other mechanical mechanismsto store or release energy. One or more energy sources can be combinedinto a single device. Devices can further include gears, valves, orother mechanisms to convert energy into movement of one or morecomponents of a device.

The one or more automated functions of an auto-injector may be activatedvia an activation mechanism. Such an activation mechanism can includeone or more of a button, a lever, a needle sleeve, or other activationcomponent. Activation may be a one-step or multi-step process. That is,a user may need to activate one or more activation mechanism in order tocause the automated function. For example, a user may depress a needlesleeve against their body in order to cause injection of a medicament.In other devices, a user may be required to depress a button and retracta needle shield in order to cause injection.

In addition, such activation may activate one or more mechanisms. Forexample, an activation sequence may activate at least two of needleinsertion, medicament injection, and needle retraction. Some devices mayalso require a specific sequence of steps to cause the one or moreautomated functions to occur. Other devices may operate with sequenceindependent steps.

Some delivery devices can include one or more functions of a safetysyringe, pen-injector, or auto-injector. For example, a delivery devicecould include a mechanical energy source configured to automaticallyinject a medicament (as typically found in an auto-injector) and a dosesetting mechanism (as typically found in a pen-injector).

Further scope of applicability of the present disclosure will becomeapparent from the detailed description given hereinafter. However, itshould be understood that the detailed description and specificexamples, while indicating exemplary embodiments of the disclosure, aregiven by way of illustration only, since various changes andmodifications within the spirit and scope of the disclosure will becomeapparent to those skilled in the art from this detailed description.

BRIEF DESCRIPTION OF THE FIGURES

The present disclosure will become more fully understood from thedetailed description given below and the accompanying drawings, whichare given by way of illustration only, and do not limit the presentdisclosure, and wherein:

FIG. 1 is a schematic view of an exemplary embodiment of a drug deliverydevice,

FIG. 2 is a schematic perspective exploded view of a drive subassemblyof a drug delivery device,

FIG. 3 is a schematic side view of the drive subassembly,

FIG. 4 is a schematic detail view of the drive subassembly showing aplunger release mechanism,

FIG. 5 is a schematic view of an exemplary embodiment of the plungerrelease mechanism during assembly of the drive subassembly,

FIG. 6 is a schematic view of the plunger release mechanism during finalassembly,

FIG. 7 is a schematic view of the plunger release mechanism after finalassembly,

FIG. 8 is a schematic view of the plunger release mechanism afterdepression of a sleeve,

FIG. 9 is a schematic detail view of the plunger release mechanism afterfinal assembly and prior to depression of the sleeve,

FIG. 10 is a schematic detail view of the plunger release mechanismduring depression of the sleeve, and

FIG. 11 is a schematic detail view of another embodiment of the plungerrelease mechanism during depression of the sleeve.

Corresponding parts are marked with the same reference symbols in allfigures.

DETAILED DESCRIPTION

According to some embodiments of the present disclosure, an exemplarydrug delivery device 10 is shown in FIGS. 1A and 1B. Device 10, asdescribed above, is configured to inject a drug or medicament into apatient's body.

Device 10 includes a housing 11 which typically contains a reservoircontaining the medicament to be injected (e.g., a syringe 24 or acontainer) and the components required to facilitate one or more stepsof the delivery process.

Device 10 can also include a cap assembly 12 that can be detachablymounted to the housing 11, in particular on a distal or front end D ofthe device 10. Typically, a user must remove cap assembly or cap 12 fromhousing 11 before device 10 can be operated.

As shown, housing 11 is substantially cylindrical and has asubstantially constant diameter along the longitudinal axis X. Thehousing 11 has a distal region 20 and a proximal region 21. The term“distal” refers to a location that is relatively closer to a site ofinjection, and the term “proximal” refers to a location that isrelatively further away from the injection site.

Device 10 can also include a needle sleeve 13 coupled to the housing 11to permit movement of the sleeve 13 relative to the housing 11. Forexample, the sleeve 13 can move in a longitudinal direction parallel tolongitudinal axis X. Specifically, movement of the sleeve 13 in aproximal direction can permit a needle 17 to extend from distal region20 of housing 11.

Insertion of the needle 17 can occur via several mechanisms. Forexample, the needle 17 may be fixedly located relative to housing 11 andinitially be located within an extended needle sleeve 13. Proximalmovement of the sleeve 13 by placing a distal end of sleeve 13 against apatient's body and moving housing 11 in a distal direction will uncoverthe distal end of needle 17. Such relative movement allows the distalend of needle 17 to extend into the patient's body. Such insertion istermed “manual” insertion as the needle 17 is manually inserted via thepatient's manual movement of the housing 11 relative to the sleeve 13.

Another form of insertion is “automated,” whereby the needle 17 movesrelative to housing 11. Such insertion can be triggered by movement ofsleeve 13 or by another form of activation, such as, for example, abutton 22. As shown in FIGS. 1A & 1B, button 22 is located at a proximalor back end P of the housing 11. However, in other embodiments, button22 could be located on a side of housing 11. In further embodiments, thebutton 22 has been deleted and is replaced for instance by a sleevetrigger mechanism, e.g. provided by pushing the needle sleeve 13 insidethe housing when the drug delivery device is put onto an injection side.

Other manual or automated features can include drug injection or needleretraction, or both. Injection is the process by which a bung or piston23 is moved from a proximal location within a container or syringe 24 toa more distal location within the syringe 24 in order to force amedicament from the syringe 24 through needle 17.

In some embodiments, an energy source, e.g. a drive spring 30 isarranged in a plunger 40 and is under compression before device 10 isactivated. A proximal end of the drive spring 30 can be fixed withinproximal region 21 of housing 11, and a distal end of the drive spring30 can be configured to apply a compressive force to a proximal surfaceof piston 23. Following activation, at least part of the energy storedin the drive spring 30 can be applied to the proximal surface of piston23. This compressive force can act on piston 23 to move it in a distaldirection. Such distal movement acts to compress the liquid medicamentwithin the syringe 24, forcing it out of needle 17.

Following injection, the needle 17 can be retracted within sleeve 13 orhousing 11. Retraction can occur when sleeve 13 moves distally as a userremoves device 10 from a patient's body. This can occur as needle 17remains fixedly located relative to housing 11. Once a distal end of thesleeve 13 has moved past a distal end of the needle 17, and the needle17 is covered, the sleeve 13 can be locked. Such locking can includelocking any proximal movement of the sleeve 13 relative to the housing11.

Another form of needle retraction can occur if the needle 17 is movedrelative to the housing 11.

Such movement can occur if the syringe within the housing 11 is moved ina proximal direction relative to the housing 11. This proximal movementcan be achieved by using a retraction spring (not shown), located in thedistal region 20. A compressed retraction spring, when activated, cansupply sufficient force to the syringe 24 to move it in a proximaldirection. Following sufficient retraction, any relative movementbetween the needle 17 and the housing 11 can be locked with a lockingmechanism. In addition, button 22 or other components of device 10 canbe locked as required.

In some embodiments, the housing may comprise a window 11 a throughwhich the syringe 24 can be monitored.

The drug delivery device 10 may be divided in two subassemblies, acontrol subassembly and a drive subassembly 10.1. This allows forimproving flexibility as to the time and location of manufacture of thesubassemblies and final assembly with the syringe 24.

FIG. 2 is a perspective exploded view of the drive subassembly 10.1. Thedrive subassembly 10.1 comprises components used to displace themedicament from the syringe 24. If the viscosity or volume of themedicament M in the syringe 24 is varied, only parts of the drivesubassembly 10.1 may need to be changed. The drive subassembly 10.1comprises the plunger 40, the drive spring 30 and the proximal region 21of the housing 11. In an exemplary embodiment, the drive subassembly10.1 may be assembled in a process which requires virtually only axialmotion except for the plunger 40. In order to assemble the drivesubassembly 10.1 the drive spring 30 is inserted into the plunger 40 andthe plunger 40 is inserted in the proximal region 21 in the proximaldirection P thereby compressing the drive spring 30. Once the plunger 40reaches a compressed position it is rotated by an angle, e.g.approximately 30° to lock it to the proximal region 21. In an exemplaryembodiment the proximal region 21 could have a cam surface which couldinduce this rotation prior to the plunger 40 reaching the compressedposition.

Furthermore, a feedback element 50, e.g. a spring element may beprovided to indicate an event, e.g. an end of dose, by providing anaudible and/or tactile feedback.

FIG. 3 is a schematic side view of the drive subassembly 10.1. FIGS. 4Aand 4B are schematic detail views of the drive subassembly 10.1 showingpart of a plunger release mechanism 25.

The plunger release mechanism 25 controls the activation of syringeemptying. The plunger release mechanism 25 is adapted to release theplunger 40 once the sleeve 13 is depressed and reaches a retractedposition RP within the housing 11.

The plunger release mechanism 25 comprises a first plunger boss 40.1arranged on the plunger 40 and a profiled slot 21.1 in the proximalregion 21 of the housing 11. The profiled slot 21.1 comprises a firstangled surface 21.2 adapted to engage the first plunger boss 40.1 toinduce a torque in a first rotational direction R1 to the plunger 40, awall 21.3 for limiting movement of the first plunger boss 40.1 in thefirst rotational direction R1 when engaged to the first angled surface21.2. Furthermore, the profiled slot 21.1 comprises a second angledsurface 21.4 adapted to engage the first plunger boss 40.1 to induce atorque in the first rotational direction R1 to the plunger 40.

The first angled surface 21.2 and/or the second angled surface 21.4 mayhave an angle in a range from 30° to 70° relative to a perpendicular onthe longitudinal axis X of the drug delivery device 10 which may also bethe longitudinal axis of the plunger 40.

In a first state shown in FIG. 4A, the first plunger boss 40.1 isengaged to the first angled surface 21.2. Due to the drive spring 30acting on the plunger 40, the first plunger boss 40.1 is pressed againstthe first angled surface 21.2 in a distal direction D such that a torqueis induced to the plunger 40 in the first rotational direction R1 sothat the first plunger boss 40.1 slides along the first angled surface21.2 until it abuts the wall 21.3 so that rotation of the plunger 40 inthe first rotational direction R1 is halted.

FIG. 4B shows the plunger release mechanism 25 in a second state.Starting from the first state, the plunger 40 has been moved a distanceat least as long as the wall 21.3 in the proximal direction P such thatthe wall 21.3 no longer limits movement of the first plunger boss 40.1in the first rotational direction R1. The plunger 40 has then beenrotated further in the first rotational direction R1 so that the firstplunger boss 40.1 engages the second angled surface 21.4. Due to thedrive spring 30 acting on the plunger 40, the first plunger boss 40.1 ispressed against the second angled surface 21.4 in a distal direction Dsuch that a torque is induced to the plunger 40 in the first rotationaldirection R1 so that the first plunger boss 40.1 slides along the secondangled surface 21.4. If the plunger 40 is not otherwise prevented fromrotating further, the first plunger boss 40.1 may slide down the secondangled surface 21.4 until disengaging it, allowing the plunger 40 toadvance in the distal direction D to displace the medicament from thesyringe 24.

In an exemplary embodiment, movement of the plunger 40 from the firststate in the proximal direction P and onto the second angled surface21.4 may be achieved by the sleeve 13 interacting with the plunger 40,e.g. by engaging the first plunger boss 40.1 or a further plunger bossor rib on the plunger (not shown).

An exemplary embodiment of the plunger release mechanism 25 is shown inmore detail in FIGS. 5, 6, 7 and 8 .

FIG. 5 shows the plunger release mechanism during assembly of the drivesubassembly 10.1.

The plunger release mechanism 25 is adapted to release the plunger 40once the sleeve 13 is depressed and reaches a retracted position withinthe housing 11.

The plunger release mechanism 25 comprises the plunger 40, the proximalregion 21, and the sleeve 13 interacting with each other. The sleeve 13and the proximal region 21 are configured to move only in parallel withthe longitudinal axis X relative to each other whereas the plunger 40can move both in parallel with the longitudinal axis X and rotate aboutthe longitudinal axis X. The parts of the plunger release mechanism 25may be essentially rigid and require no deformation in order to functioncorrectly.

The parts arranged for engaging the plunger 40, proximal region 21 andsleeve 13 comprise: a first plunger boss 40.1 on the plunger 40, asecond plunger boss 40.2 on the plunger 40, an angled plunger rib 40.3on the plunger 40, a profiled slot 21.1 in the proximal region 21adapted to interact with the first plunger boss 40.1, a sleeve rib 13.1on the sleeve 13 comprising a proximal face 13.2 adapted to interactwith the angled plunger rib 40.3, a distal face 13.3 and a longitudinalface 13.4 adapted to interact with the second plunger boss 40.2.

The profiled slot 21.1 comprises a first angled surface 21.2 adapted toengage the first plunger boss 40.1 to induce a torque in a firstrotational direction R1 to the plunger 40, a wall 21.3 for limitingmovement of the first plunger boss 40.1 in the first rotationaldirection R1 when engaged to the first angled surface 21.2. Furthermore,the profiled slot 21.1 comprises a second angled surface 21.4 adapted toengage the first plunger boss 40.1 to induce a torque in the firstrotational direction R1 to the plunger 40.

During assembly of the drive subassembly 10.1 the plunger 40 with thedrive spring 30 is inserted into the proximal region 21. Once theplunger 40 reaches a proximal position the first plunger boss 40.1 isaxially aligned with the profiled slot 21.1. By rotating the plunger 40in a second rotational direction R2 by an angle, e.g. approximately 30°,the first plunger boss 40.1 is moved into the profiled slot 21.1. Inthis position the first angled surface 21.2 moves the first plunger boss40.1 against the wall 21.3 by inducing a torque to the plunger 40 in thefirst rotational direction R1 due to the drive spring 30 biasing theplunger 40 in the distal direction D.

In order to assemble the drug delivery device 10, a syringe 24 may beinserted into the control subassembly which may comprise the distalregion 20 of the housing 11.

Afterwards, the drive subassembly 10.1 is inserted into the controlsubassembly in the distal direction D. The proximal region 21 and thedistal region 20 may comprise snap connections to lock them togetherwhen assembled. During the final assembly of the drug delivery device 10the sleeve 13 may be partially depressed to allow initiation of theplunger release mechanism 25, e.g. by an assembly jig (not illustrated)or in a different way.

FIG. 6 shows the plunger release mechanism 25 during the final assembly.The sleeve rib 13.1 proximally abuts the angled plunger rib 40.3 therebyinducing a torque to the plunger 40 in the first rotational direction R1and pushing the plunger 40 in the proximal direction P so that the firstplunger boss 40.1 moves along the wall 21.3 until it disengages from thewall 21.3. Due to the induced torque, the first plunger boss 40.1 movesin the first rotational direction R1 and engages the second angledsurface 21.4. The depression of the sleeve 13 may cease and, due to thefirst plunger boss 40.1 engaging the second angled surface 21.4 and thedrive spring 30 acting on the plunger 40 in the distal direction D, theplunger 40 rotates further in the first rotational direction R1. As thesleeve 13 is not being depressed further it may move in the distaldirection D relative to the housing 11, e.g. under the action of asleeve spring (not illustrated). This movement is limited by the secondplunger boss 40.2 abutting the distal face 13.3 on the sleeve rib 13.1.Further rotation of the plunger 40 in the first rotational direction R1is prevented by the second plunger boss 40.2 abutting the longitudinalface 13.4 of the sleeve rib 13.1. The load of the drive spring 30 isresolved within the proximal region 21 by the first plunger boss 40.1engaging the profiled slot 21.1. This state of the plunger releasemechanism 25 is illustrated in FIG. 7 .

A sequence of operation of the drug delivery device 10 may be asfollows:

The user removes the cap assembly 12 pulling it in the distal directionD away from the housing 11. Removal of the cap assembly 12 may at thesame time remove a protective needle sheath from the needle 17.

The sleeve 13 is in an extended position protruding from the housing 11in the distal direction

D. The extended position may be defined by the second plunger boss 40.2proximally abutting the distal face 13.3 of the sleeve rib 13.1.

The user may then press the drug delivery device 10 with the sleeve 13ahead against an injection site, e.g. a patient's skin thereby movingthe sleeve 13 from the extended position towards a retracted positionagainst the bias of the shroud spring.

FIG. 8 is a schematic view of the plunger release mechanism 25 afterdepression of the sleeve 13 into the retracted position. As the sleeve13 is being moved from the extended position towards the retractedposition the second plunger boss 40.2 moves (starting from the positionshown in FIG. 7 ) relative to the sleeve 13 in the distal direction Dguided along the longitudinal face 13.4 of the sleeve rib 13.1.

In an exemplary embodiment the longitudinal face 13.4 of the sleeve rib13.1 may comprise an interruption or bump feature (not illustrated) forcreating an increase in the force required to depress the sleeve 13further. This may be used to indicate to the user that needle insertionwould commence with further depression of the sleeve 13. Up until thispoint, the user is free to remove the drug delivery device 10 from theinjection site and reposition as the sleeve 13 will re-extend to itsinitial position under the force of the shroud spring.

If the user continues pressing the drug delivery device 10 against theinjection site the sleeve 13 is moved into the retracted positionexposing the needle 17 and inserting it into the injection site.

Once the sleeve 13 is depressed into the retracted position, and theneedle 17 inserted, the second plunger boss 40.2 has moved distallybeyond the sleeve rib 13.1 such that the plunger 40 is no longerprevented from rotating in the first rotational direction R1 due to thetorque induced by the drive spring 30 and the first plunger boss 40.1engaging the second angled surface 21.4 on the profiled slot 21.1. Theplunger 40 rotates in the first rotational direction R1 due to thistorque and the first plunger boss 40.1 comes clear of the profiled slot21.1. The plunger 40 is thus released and advances the piston 23 in thedistal direction D displacing the medicament from the syringe 24 throughthe needle 17. The release of the first or second plunger boss 40.1,40.2 may provide audible feedback that delivery of the medicament hasstarted.

FIG. 9 is a schematic detail view of the plunger release mechanism 25after final assembly and prior to depression of the sleeve 13. Movementof the sleeve 13 in the distal direction D relative to the housing 11 islimited by the second plunger boss 40.2 abutting the distal face 13.3 onthe sleeve rib 13.1. Further rotation of the plunger 40 in the firstrotational direction R1 is prevented by the second plunger boss 40.2abutting the longitudinal face 13.4 of the sleeve rib 13.1.

FIG. 10 is a schematic detail view of the plunger release mechanism 25during depression of the sleeve 13. As the sleeve 13 is being moved fromthe extended position towards the retracted position in the proximaldirection P the second plunger boss 40.2 moves (starting from theposition shown in FIG. 9 ) relative to the sleeve 13 in the distaldirection D guided along the longitudinal face 13.4 of the sleeve rib13.1.

If the user continues pressing the drug delivery device 10 against theinjection site the sleeve 13 is moved into the retracted positionexposing the needle 17 and inserting it into the injection site.

Once the sleeve 13 is depressed into the retracted position, and theneedle 17 inserted, the second plunger boss 40.2 has moved distallybeyond the sleeve rib 13.1 such that the plunger 40 is no longerprevented from rotating in the first rotational direction R1 due to thetorque induced by the drive spring 30 and the first plunger boss 40.1engaging the second angled surface 21.4 on the profiled slot 21.1. Theplunger 40 rotates in the first rotational direction R1 due to thistorque and the first plunger boss 40.1 comes clear of the profiled slot21.1. The plunger 40 is thus released and advances the piston 23 in thedistal direction D displacing the medicament from the syringe 24 throughthe needle 17.

FIG. 11 is a schematic detail view of another embodiment of the plungerrelease mechanism 25 during depression of the sleeve 13. In addition tothe embodiment described above, a sleeve ramp 13.5 is provided on thesleeve 13. As the sleeve 13 approaches the retracted position, thesleeve ramp 13.5 engages a projection such as a rib or boss on theplunger 40, e.g. the angled plunger rib 40.3 to actively rotate theplunger 40 in the first rotational direction R1. If the plunger 40should not rotate spontaneously due to the features of the previousembodiments, the additional sleeve ramp 13.5 will induce rotation of theplunger 40.

During normal use, the plunger 40 will release as in the previousembodiments. The sleeve ramp 13.5 is positioned to only interact withthe angled plunger rib 40.3 if the plunger 40 has not spontaneouslyrotated near the end of the depression of the sleeve 13. The skilledperson will readily understand that the embodiment of FIG. 11 wouldlikewise work if only one of the rib or boss on the plunger 40, e.g. theangled plunger rib 40.3, or the sleeve ramp 13.5 was ramped or angled.

Another benefit of the embodiment of FIG. 11 is that it providesadditional guidance of the plunger 40 movement as it activates.

In another exemplary embodiment, the sleeve ramp 13.5 engaging the ribor boss on the plunger 40, e.g. the angled plunger rib 40.3, may be theonly way to rotate the plunger 40 out of engagement with the profiledslot 21.1. For example, the profiled slot 21.1 may not have an angledsurface causing the plunger 40 to rotate in the first rotationaldirection R1 out of engagement with the profiled slot 21.1. In anexemplary embodiment, the profiled slot 21.1 may only have a transversalsurface towards the distal direction D and transversally orientedrelative to the longitudinal axis X. The transversal surface may have adetent or bump. In another exemplary embodiment the profiled slot 21.1may only have an angled surface causing the plunger to rotate in thesecond rotational direction R2 maintaining the first plunger boss 40.1engaged within the profiled slot 21.1.

In an exemplary embodiment, the drug delivery device 10 may be anauto-injector.

The terms “drug” or “medicament” are used herein to describe one or morepharmaceutically active compounds. As described below, a drug ormedicament can include at least one small or large molecule, orcombinations thereof, in various types of formulations, for thetreatment of one or more diseases. Exemplary pharmaceutically activecompounds may include small molecules; polypeptides, peptides andproteins (e.g., hormones, growth factors, antibodies, antibodyfragments, and enzymes); carbohydrates and polysaccharides; and nucleicacids, double or single stranded DNA (including naked and cDNA), RNA,antisense nucleic acids such as antisense DNA and RNA, small interferingRNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids maybe incorporated into molecular delivery systems such as vectors,plasmids, or liposomes. Mixtures of one or more of these drugs are alsocontemplated.

The term “drug delivery device” shall encompass any type of device orsystem configured to dispense a drug into a human or animal body.Without limitation, a drug delivery device may be an injection device(e.g., syringe, pen injector, auto injector, large-volume device, pump,perfusion system, or other device configured for intraocular,subcutaneous, intramuscular, or intravascular delivery), skin patch(e.g., osmotic, chemical, micro-needle), inhaler (e.g., nasal orpulmonary), implantable (e.g., coated stent, capsule), or feedingsystems for the gastro-intestinal tract. The presently described drugsmay be particularly useful with injection devices that include a needle,e.g., a small gauge needle.

The drug or medicament may be contained in a primary package or “drugcontainer” adapted for use with a drug delivery device. The drugcontainer may be, e.g., a cartridge, syringe, reservoir, or other vesselconfigured to provide a suitable chamber for storage (e.g., short- orlong-term storage) of one or more pharmaceutically active compounds. Forexample, in some instances, the chamber may be designed to store a drugfor at least one day (e.g., 1 to at least 30 days). In some instances,the chamber may be designed to store a drug for about 1 month to about 2years. Storage may occur at room temperature (e.g., about 20° C.), orrefrigerated temperatures (e.g., from about −4° C. to about 4° C.). Insome instances, the drug container may be or may include a dual-chambercartridge configured to store two or more components of a drugformulation (e.g., a drug and a diluent, or two different types ofdrugs) separately, one in each chamber. In such instances, the twochambers of the dual-chamber cartridge may be configured to allow mixingbetween the two or more components of the drug or medicament prior toand/or during dispensing into the human or animal body. For example, thetwo chambers may be configured such that they are in fluid communicationwith each other (e.g., by way of a conduit between the two chambers) andallow mixing of the two components when desired by a user prior todispensing. Alternatively or in addition, the two chambers may beconfigured to allow mixing as the components are being dispensed intothe human or animal body.

The drug delivery devices and drugs described herein can be used for thetreatment and/or prophylaxis of many different types of disorders.Exemplary disorders include, e.g., diabetes mellitus or complicationsassociated with diabetes mellitus such as diabetic retinopathy,thromboembolism disorders such as deep vein or pulmonarythromboembolism. Further exemplary disorders are acute coronary syndrome(ACS), angina, myocardial infarction, cancer, macular degeneration,inflammation, hay fever, atherosclerosis and/or rheumatoid arthritis.

Exemplary drugs for the treatment and/or prophylaxis of diabetesmellitus or complications associated with diabetes mellitus include aninsulin, e.g., human insulin, or a human insulin analogue or derivative,a glucagon-like peptide (GLP-1), GLP-1 analogues or GLP-1 receptoragonists, or an analogue or derivative thereof, a dipeptidyl peptidase-4(DPP4) inhibitor, or a pharmaceutically acceptable salt or solvatethereof, or any mixture thereof. As used herein, the term “derivative”refers to any substance which is sufficiently structurally similar tothe original substance so as to have substantially similar functionalityor activity (e.g., therapeutic effectiveness).

Exemplary insulin analogues are Gly(A21), Arg(B31), Arg(B32) humaninsulin (insulin glargine); Lys(B3), Glu(B29) human insulin; Lys(B28),Pro(B29) human insulin; Asp(B28) human insulin;

human insulin, wherein proline in position B28 is replaced by Asp, Lys,Leu, Val or Ala and wherein in position B29 Lys may be replaced by Pro;Ala(B26) human insulin; Des(B28-B30) human insulin; Des(B27) humaninsulin and Des(B30) human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des(B30)human insulin; B29-N-palmitoyl-des(B30) human insulin; B29-N-myristoylhuman insulin; B29-N-palmitoyl human insulin; B28-N-myristoylLysB28ProB29 human insulin; B28-N-palmitoyl-LysB28ProB29 human insulin;B30-N-myristoyl-ThrB29LysB30 human insulin; B30-N-palmitoyl-ThrB29LysB30 human insulin; B29-N-(N-palmitoyl-gamma-glutamyl)-des(B30)human insulin; B29-N-(N-lithocholyl-gamma-glutamyl)-des(B30) humaninsulin; B29-N-(ω-carboxyheptadecanoyl)-des(B30) human insulin andB29-N-(ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1analogues and GLP-1 receptor agonists are, for example:Lixisenatide/AVE0010/ZP10/Lyxumia,Exenatide/Exendin-4/Byetta/Bydureon/ITCA 650/AC-2993 (a 39 amino acidpeptide which is produced by the salivary glands of the Gila monster),Liraglutide/Victoza, Semaglutide, Taspoglutide, Syncria/Albiglutide,Dulaglutide, rExendin-4, CJC-1134-PC, PB-1023, TTP-054,Langlenatide/HM-11260C, CM-3, GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926,NN-9927, Nodexen, Viador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697,DA-3091, MAR-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030,CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN andGlucagon-Xten.

An exemplary oligonucleotide is, for example: mipomersen/Kynamro, acholesterol-reducing antisense therapeutic for the treatment of familialhypercholesterolemia.

Exemplary DPP4 inhibitors are Vildagliptin, Sitagliptin, Denagliptin,Saxagliptin, Berberine.

Exemplary hormones include hypophysis hormones or hypothalamus hormonesor regulatory active peptides and their antagonists, such asGonadotropine (Follitropin, Lutropin, Choriongonadotropin, Menotropin),Somatropine (Somatropin), Desmopressin, Terlipressin, Gonadorelin,Triptorelin, Leuprorelin, Buserelin, Nafarelin, and Goserelin.

Exemplary polysaccharides include a glucosaminoglycane, a hyaluronicacid, a heparin, a low molecular weight heparin or an ultra-lowmolecular weight heparin or a derivative thereof, or a sulphatedpolysaccharide, e.g. a poly-sulphated form of the above-mentionedpolysaccharides, and/or a pharmaceutically acceptable salt thereof. Anexample of a pharmaceutically acceptable salt of a poly-sulphated lowmolecular weight heparin is enoxaparin sodium. An example of ahyaluronic acid derivative is Hylan G-F 20/Synvisc, a sodiumhyaluronate.

The term “antibody”, as used herein, refers to an immunoglobulinmolecule or an antigen-binding portion thereof. Examples ofantigen-binding portions of immunoglobulin molecules include F(ab) andF(ab′)₂ fragments, which retain the ability to bind antigen. Theantibody can be polyclonal, monoclonal, recombinant, chimeric,de-immunized or humanized, fully human, non-human, (e.g., murine), orsingle chain antibody. In some embodiments, the antibody has effectorfunction and can fix complement. In some embodiments, the antibody hasreduced or no ability to bind an Fc receptor. For example, the antibodycan be an isotype or subtype, an antibody fragment or mutant, which doesnot support binding to an Fc receptor, e.g., it has a mutagenized ordeleted Fc receptor binding region.

The terms “fragment” or “antibody fragment” refer to a polypeptidederived from an antibody polypeptide molecule (e.g., an antibody heavyand/or light chain polypeptide) that does not comprise a full-lengthantibody polypeptide, but that still comprises at least a portion of afull-length antibody polypeptide that is capable of binding to anantigen. Antibody fragments can comprise a cleaved portion of a fulllength antibody polypeptide, although the term is not limited to suchcleaved fragments. Antibody fragments that are useful in the presentdisclosure include, for example, Fab fragments, F(ab′)2 fragments, scFv(single-chain Fv) fragments, linear antibodies, monospecific ormultispecific antibody fragments such as bispecific, trispecific, andmultispecific antibodies (e.g., diabodies, triabodies, tetrabodies),minibodies, chelating recombinant antibodies, tribodies or bibodies,intrabodies, nanobodies, small modular immunopharmaceuticals (SMIP),binding-domain immunoglobulin fusion proteins, camelized antibodies, andVHH containing antibodies. Additional examples of antigen-bindingantibody fragments are known in the art.

The terms “Complementarity-determining region” or “CDR” refer to shortpolypeptide sequences within the variable region of both heavy and lightchain polypeptides that are primarily responsible for mediating specificantigen recognition. The term “framework region” refers to amino acidsequences within the variable region of both heavy and light chainpolypeptides that are not CDR sequences, and are primarily responsiblefor maintaining correct positioning of the CDR sequences to permitantigen binding. Although the framework regions themselves typically donot directly participate in antigen binding, as is known in the art,certain residues within the framework regions of certain antibodies candirectly participate in antigen binding or can affect the ability of oneor more amino acids in CDRs to interact with antigen.

Exemplary antibodies are anti PCSK-9 mAb (e.g., Alirocumab), anti IL-6mAb (e.g., Sarilumab), and anti IL-4 mAb (e.g., Dupilumab).

The compounds described herein may be used in pharmaceuticalformulations comprising (a) the compound(s) or pharmaceuticallyacceptable salts thereof, and (b) a pharmaceutically acceptable carrier.The compounds may also be used in pharmaceutical formulations thatinclude one or more other active pharmaceutical ingredients or inpharmaceutical formulations in which the present compound or apharmaceutically acceptable salt thereof is the only active ingredient.Accordingly, the pharmaceutical formulations of the present disclosureencompass any formulation made by admixing a compound described hereinand a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any drug described herein are alsocontemplated for use in drug delivery devices. Pharmaceuticallyacceptable salts are for example acid addition salts and basic salts.Acid addition salts are e.g. HCl or HBr salts. Basic salts are e.g.salts having a cation selected from an alkali or alkaline earth metal,e.g. Na+, or K+, or Ca2+, or an ammonium ion N+(R1)(R2)(R3)(R4), whereinR1 to R4 independently of each other mean: hydrogen, an optionallysubstituted C1-C6-alkyl group, an optionally substituted C2-C6-alkenylgroup, an optionally substituted C6-C10-aryl group, or an optionallysubstituted C6-C10-heteroaryl group. Further examples ofpharmaceutically acceptable salts are known to those of skill in thearts.

Pharmaceutically acceptable solvates are for example hydrates oralkanolates such as methanolates or ethanolates.

Those of skill in the art will understand that modifications (additionsand/or removals) of various components of the substances, formulations,apparatuses, methods, systems and embodiments described herein may bemade without departing from the full scope and spirit of the presentdisclosure, which encompass such modifications and any and allequivalents thereof.

LIST OF REFERENCES

-   10 drug delivery device-   10.1 drive subassembly-   11 housing-   11a window-   12 cap assembly-   13 sleeve-   13.1 sleeve rib-   13.2 proximal face-   13.3 distal face-   13.4 longitudinal face-   13.5 sleeve ramp-   17 needle-   20 distal region-   21 proximal region-   21.1 profiled slot-   21.2 first angled surface-   21.3 wall-   21.4 second angled surface-   22 button-   23 piston-   24 syringe-   25 plunger release mechanism-   30 drive spring-   40 plunger-   40.1 first plunger boss-   40.2 second plunger boss-   40.3 angled plunger rib-   D distal end, distal direction-   P proximal end, proximal direction-   R1 first rotational direction-   R2 second rotational direction-   X longitudinal axis

The invention claimed is:
 1. A drug delivery device comprising: ahousing adapted to receive a medicament container; a sleeve coupled tothe housing to permit movement of the sleeve relative to the housing; aplunger; and a plunger release mechanism adapted to release the plungeronce the sleeve is depressed to a retracted position, the plungerrelease mechanism comprising: a first plunger boss arranged on theplunger; a profiled slot arranged on the housing and adapted to beengaged by the first plunger boss to inhibit movement of the plunger ina distal direction, wherein the plunger is rotatable about alongitudinal axis to release the first plunger boss from the profiledslot to allow movement of the plunger in the distal direction; and thesleeve comprising a sleeve ramp adapted to engage a projection on theplunger to rotate the plunger to release the first plunger boss from theprofiled slot when the sleeve is moved in a proximal direction, whereinthe sleeve ramp is positioned so as to only interact with the projectionon the plunger if the plunger has not spontaneously rotated when thesleeve is depressed to the retracted position, wherein the profiled slotis adapted to induce a torque to the plunger when an axial force isapplied to the plunger, wherein the profiled slot comprises at least oneangled surface adapted to engage the first plunger boss to induce atorque in a first rotational direction to the plunger to release thefirst plunger boss from the profiled slot, and wherein the first plungerboss is configured to slide down the angled surface until disengagingwith the angled surface so as to allow the movement of the plunger inthe distal direction.
 2. The drug delivery device of claim 1, whereinthe profiled slot further comprises: a wall adapted to limit movement ofthe first plunger boss in the first rotational direction when engaged toa first angled surface; and a second angled surface adjacent the walland adapted to induce the torque in the first rotational direction tothe plunger to release the first plunger boss from the profiled slot. 3.The drug delivery device according to claim 2, wherein the first angledsurface and/or the second angled surface are/is oriented at an anglefrom 20° to 60° relative to the wall of the profiled slot.
 4. The drugdelivery device according to claim 2, wherein the release of the firstplunger boss from the first angled surface and/or from the second angledsurface provides an audible feedback.
 5. The drug delivery deviceaccording to claim 1, wherein the housing comprises a distal region anda proximal region, and the proximal region comprises the profiled slotand wherein the projection of the plunger is adapted to abut a sleeverib of the sleeve upon coupling of the proximal region with the plungerand a drive spring to the distal region for moving the first plungerboss from a first angled surface of the profiled slot to a second angledsurface of the profiled slot.
 6. The drug delivery device according toclaim 1, further comprising a second plunger boss arranged on theplunger and a sleeve rib arranged on the sleeve, the sleeve rib having alongitudinal face adapted to engage the second plunger boss preventingrotation of the plunger in the first rotational direction to keep thefirst plunger boss engaged to the at least one angled surface, whereinthe sleeve rib is adapted to disengage the second plunger boss when thesleeve rib is moved in a proximal direction thereby allowing the plungerto rotate in the first rotational direction and the first plunger bossto disengage a second angled surface.
 7. The drug delivery deviceaccording to claim 6, wherein a release of the second plunger boss ofthe plunger from the sleeve rib provides an audible feedback.
 8. Thedrug delivery device according to claim 1, wherein the projection isadapted to abut a sleeve rib to induce a torque to the plunger in thefirst rotational direction and push the plunger in the proximaldirection when the first plunger boss is engaged to a first angledsurface and to a wall of the profiled slot.
 9. The drug delivery deviceaccording to claim 1, wherein a sleeve rib of the sleeve comprises adistal face adapted to engage a second plunger boss of the plunger tolimit movement of the sleeve rib in a distal direction relative to theplunger.
 10. The drug delivery device according to claim 1, wherein asleeve rib of the sleeve is adapted to disengage a second plunger bossof the plunger before the sleeve ramp engages a projection on theplunger when the sleeve rib is moved in the proximal direction.
 11. Thedrug delivery device according to claim 1, wherein a drive spring isarranged within the housing and adapted to bias the plunger in thedistal direction for displacing a piston of a medicament container. 12.The drug delivery device according to claim 11, wherein the plunger ishollow and the drive spring is arranged within the plunger.
 13. The drugdelivery device according to claim 1, wherein the housing comprises adistal region and a proximal region, and the proximal region comprisesthe profiled slot.
 14. The drug delivery device according to claim 13,wherein the projection is adapted to abut a sleeve rib of the sleeveupon coupling of the proximal region with the plunger and a drive springto the distal region for moving the first plunger boss from a firstangled surface of the profiled slot to a second angled surface of theprofiled slot.
 15. The drug delivery device according to claim 1,further comprising a medicament container containing a medicament. 16.The drug delivery device according to claim 1, wherein the projection isa rib or boss.
 17. The drug delivery device according to claim 1,wherein the projection is a plunger rib.
 18. A method comprising:engaging, under an action of a plunger spring, a first plunger boss of aplunger against an angled surface of a profiled slot of a housing of adrug delivery device causing the first plunger boss to slide along theangled surface of the profiled slot until a wall of the profiled slot isengaged inhibiting a rotation of the plunger and inhibiting a distalmovement of the plunger; disengaging the first plunger boss from theangled surface and the wall to allow rotation of the plunger; andengaging a projection of the plunger with a sleeve ramp of a sleeve torotate the plunger, thereby allowing the first plunger boss to disengagefrom the profiled slot and allowing the plunger spring to push theplunger in a distal direction to expel medicament from the drug deliverydevice.
 19. A drug delivery device comprising: a plunger movable along alongitudinal axis of the drug delivery device, rotatable about thelongitudinal axis relative to a housing of the drug delivery device, andcomprising a first plunger boss; a profiled slot defined by the housingand adapted to receive the first plunger boss of the plunger and adaptedto inhibit a rotation and a distal movement of the plunger when thefirst plunger boss is disposed in a first portion of the profiled slot;and a sleeve movable along the longitudinal axis and comprising a sleeveramp configured such that proximal engagement of the sleeve ramp with aprojection of the plunger causes a rotation of the plunger, allowing thefirst plunger boss to be released from the profiled slot and allowingthe plunger to move in a distal direction to expel medicament from thedrug delivery device.
 20. The drug delivery device according to claim19, wherein the profiled slot further comprises a wall adapted to limitrotational movement of the first plunger boss in a first rotationaldirection when engaged to a first angled surface and allow rotationalmovement of the first plunger boss in a second rotational direction whenengaged to the first angled surface.